Project summary There is a growing body of evidence that obesity is associated with reduced cerebral metabolism; however, the underlying mechanisms and the functional clinical implications of these observations remain unclear. The central goal of this project is to investigate a finding we have recently made that obesity is associated with decreased transport capacity for glucose across the blood-brain barrier. This proposal uses state of the art neuroimaging technology coupled with classic human metabolic phenotyping methodologies to investigate the underlying mechanisms behind how the brain is impacted by obesity. Because the brain is exquisitely sensitive to circulating glucose levels, the findings from this proposed study will help clarify how diminished brain glucose transport in obesity may lead to diminished post-prandial satiety signaling and/or be a potential mechanism for the neurocognitive consequences of obesity. The proposed studies in this R03 proposal will lay the foundation for future studies targeting brain glucose transport and metabolism alterations to treat and prevent the central nervous system complications of obesity.